The EPIC-Norfolk Study
Circulating fatty acid binding protein 4 (FABP-4) concentrations and mortality in individuals with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.
International journal of cancer 2025 ; 158: 546-559.
Pham TT, Nimptsch K, Aleksandrova K, Jenab M, Fedirko V, Olsen A, Tjønneland A, Cadeau C, Severi G, Schulze MB, Fortner RT, Katzke V, Agnoli C, Sacerdote C, Tumino R, Signoriello S, Trobajo-Sanmartín C, Gómez JH, Chirlaque MD, Sánchez MJ, Crous-Bou M, May A, Heath A, Aune D, Weiderpass E, and Pischon T
DOI : 10.1002/ijc.70090
PubMed ID : 40857027
PMCID : PMC12670333
URL : https://onlinelibrary.wiley.com/doi/10.1002/ijc.70090
Abstract
Human fatty acid binding protein-4 (FABP-4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity-mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC-specific, non-CRC-specific, and all-cause mortality by FABP-4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC and non-CRC deaths. Mediation analyses were conducted to estimate total effects (TEs), direct effects (DEs), and mediation proportions (MPs) by FABP-4 of pre-diagnostic body mass index (BMI) on mortality. In the fully adjusted model including BMI, higher circulating FABP-4 concentrations were associated with higher CRC mortality (HR = 1.49; 95% CI: 1.11-2.00) and all-cause mortality (HR = 1.49; 95% CI: 1.15-1.93), but not statistically associated with non-CRC mortality (HR = 1.51; 95% CI: 0.82-2.76). The TE and DE per 5 kg/m of BMI on all-cause mortality were 1.21; 95% CI: 1.10-1.34, and 1.13; 95% CI: 1.02-1.26, respectively, with a MP of 34.5% (p = .002) by FABP-4. For CRC-specific and non-CRC-specific mortality, MPs by FABP-4 were 33.7% (p = .03) and 36.1% (p = .02), respectively. In conclusion, higher concentrations of FABP-4 were associated with higher CRC-specific and all-cause mortality in individuals with CRC. FABP-4 was a significant partial mediator of the adiposity-mortality relationship in individuals with CRC.